SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors.

Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that the SARS-CoV-2 could also induce the development of HLA antibodies in volunteers, who donate convalescent plasma after their recovery from COVID-19. HLA antibodies have been identified as the main cause for transfusion-related acute lung injury (TRALI), a well-documented life-threatening complication of transfusions. The TRALI risk could be high in COVID-19 patients who need convalescent plasma, as such patients usually have already an impaired respiratory system affected by the SARS-CoV-2 infection. In this study, we screened 34 convalescent plasma donors on the presence of antibodies against HLA class I and II antigens. All included donors have no any history of sensitization events such as blood transfusions, pregnancy, or previous transplants. We found a high rate of HLA antibody formation in convalescent plasma donors. The frequency of positivity for HLA antibodies for class I, class II, class I and II, and the overall reactivity was 23%, 31%, 46%, and 76%, respectively. The presented data suggest a closed correlation between SARS-CoV-2 virus infection and the development of HLA antibodies in recovered convalescent plasma donors. This finding might have the potential to reduce the risk of TRALI and mortality rate in COVID-19 patients by implementing HLA diagnostic strategies before the administration of convalescent plasma.

Transfusion-related acute lung injury in a COVID-19-positive convalescent plasma recipient: a case report.

We present a case of transfusion-related acute lung injury as a complication of convalescent plasma transfusion in a patient who presented with COVID-19-related severe acute respiratory syndrome. Despite treatment with tocilizumab, remdesivir, and intravenous steroids, worsening dyspnea prompted adjunctive treatment with convalescent plasma. Two hours after completion of the plasma transfusion, the patient developed hypoxia-induced cardiac arrest secondary to transfusion-related acute lung injury. This case sheds light on life-threatening transfusion reactions and emphasizes the need to investigate post-transfusion monitoring protocols as well as the possible role of surveillance equipment.

Early safety indicators of COVID-19 convalescent plasma in 5000 patients.

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Convalescent plasma for COVID-19 complicated by ARDS due to TRALI.

Convalescent plasma, which contains antibodies from recovered individuals, has been used as an effective treatment for infectious diseases in the past and is currently being used as a potential treatment option for COVID-19. Multiple studies have reported this treatment to be safe. We report a case of a patient who developed acute respiratory distress syndrome (ARDS) with features suggestive of transfusion-related acute lung injury after being treated with convalescent plasma for COVID-19. We emphasise the need to be aware of the potential risk of transfusion reactions and disease worsening with convalescent plasma administration and to weigh the risk and benefits of this therapy before administration to patients and propose that further study be done regarding the potential risks of convalescent plasma.

Convalescent Plasma Therapy in Coronavirus Disease 2019: a Case Report and Suggestions to Overcome Obstacles.

Coronavirus disease 2019 (COVID-19) is rapidly spreading around the world, causing much morbidity and mortality everywhere. However, effective treatments or vaccines are still not available. Although convalescent plasma (CP) therapy can be useful in the treatment of COVID-19, it has not been widely used in Korea because of the concerns about adverse effects and the difficulty in matching patients to donors. The use of ABO-incompatible plasma is not contraindicated in treatment, but can be hesitated due to the lack of experience of physicians. Here, we describe a 68-year old man with COVID-19 who was treated ABO-incompatible plasma therapy; additionally, we comment on the acute side effects associated with ABO mismatch transfusion. To overcome the obstacles of donor-recipient connections (schedule and distance), we propose the storage of frozen plasma, modification of the current Blood Management Law, and the establishment of a CP bank. We suggest that experience gained in CP therapy will be useful for not only the treatment of COVID-19, but also for coping with new emerging infectious diseases.